Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains.
The voltage-sensor domain (VSD) and the ligand sensor (cytoplasmic domain) of BK channels synergistically control channel activities, thereby integrating electrical and chemical signals for cell function. Studies show that intracellular Mg2+ mediates the interaction between these sensory domains to activate the channel through an electrostatic interaction with the VSD. Here we report that Mg2+ binds to a site that consists of amino acid side chains from both the VSD (Asp99 and Asn172) and the cytoplasmic domain (Glu374 and Glu399). For each Mg2+ binding site, the residues in the VSD and those in the cytoplasmic domain come from neighboring subunits. These results suggest that the VSD and the cytoplasmic domains from different subunits may interact during channel gating, and the packing of VSD or the RCK1 domain to the pore in BK channels differ from that in Kv1.2 or MthK channels.
Yang
Huanghe
H
Department of Biomedical Engineering, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, 1 Brookings Drive, St. Louis, Missouri 63130, USA.
Shi
Jingyi
J
Zhang
Guohui
G
Yang
Junqiu
J
Delaloye
Kelli
K
Cui
Jianmin
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D021122:Protein Subunits; D008274:Magnesium